Outcomes in patients undergoing transcatheter aortic valve replacement: a sex-based story of success?
Editorial

Outcomes in patients undergoing transcatheter aortic valve replacement: a sex-based story of success?

René Vollenbroich

Department of Cardiology, Swiss Cardiovascular Center Bern, University Hospital, Bern, Switzerland

Correspondence to: René Vollenbroich, MD, MPP. Department of Cardiology, Division of Invasive Cardiology, Bern University Hospital, Freiburgstrasse 8, CH-3010 Bern, Switzerland. Email: rene.vollenbroich@insel.ch.

Provenance: This is a Guest Commentary commissioned by Section Editor Busheng Zhang, MD, PhD (Department of Cardiac Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China).

Comment on: Chandrasekhar J, Dangas G, Yu J, et al. Sex-Based Differences in Outcomes With Transcatheter Aortic Valve Therapy: TVT Registry From 2011 to 2014. J Am Coll Cardiol 2016;68:2733-44.


Submitted Apr 27, 2017. Accepted for publication May 16, 2017.

doi: 10.21037/atm.2017.06.02


Transcatheter aortic valve replacement (TAVR) has been proven to be a valuable therapeutic option in patients with severe aortic stenosis deemed at high surgical risk (1). While female patients with aortic stenosis develop a greater degree of left ventricular hypertrophy and higher relative wall thickness (2,3), the impact of these gender related pathophysiological features on outcomes after TAVR have been studied less extensively. Available data suggests that female patients are at higher risk of bleeding and vascular complications (4,5) resulting in increased rehospitalization and mortality rates as compared to male subjects (6,7). In contrast, other studies report on either improved female or gender neutral survival rates after TAVR (8-11).

The article by Chandrasekhar et al. published in the J Am Coll Cardiol Vol. 68 No. 25 presents the largest observational report on comparative outcomes in male and female patients undergoing TAVR so far. It shows data from a large registry study (n=23,652) with an appropriately equal distribution between female (49.9%) and male (51.1%) patients (12). In-hospital events derived from the Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry and one year outcomes from data of Medicare & Medicaid Services were analysed using multivariable logistic as well as Fine-Gray competing risk regression analyses. In-hospital endpoints included all-cause death, myocardial infarction (MI), stroke, major bleeding, and major vascular complications according to the Vascular Academic Research Consortium-2 definition. Major adverse cardiac events (MACE) were defined as the composite of death, MI, or stroke, whereas net adverse cardiac events (NACE) were defined as a composite of in-hospital MACE, major vascular complications, or major bleeding. On the other hand, one-year endpoints were defined through time to event occurrence of death, MI, stroke, and clinically significant bleeding.

Chandrasekhar et al. observed a different risk profile between male and female patients: while women undergoing TAVR were older and had a lower prevalence of coronary artery disease, atrial fibrillation, and diabetes, they also had a lower glomerular filtration rate, a higher rate of porcelain aorta, a higher rate of moderate to severe mitral regurgitation, and a higher mean STS score (9.0% vs. 8.0%; P<0.001). In addition, more female patients were considered to be debilitated or deconditioned by the heart team (13.7% vs. 9.1%, P<0.001) as well as frail when making the decision for a TAVR procedure. In female patients, nontransfemoral access, surgical cutdown, and smaller sheath sizes (median; 22 vs. 24 F) were more frequently used. Of note, female patients achieved a significantly higher valve cover index (≥8%; 65.7% vs. 53.9%, P<0.0001). Twice as many female patients conversed to open surgery (1.74% vs. 0.96%, P<0.0001), ventricular or annulus rupture being the most frequent underlying causes, whereas valve dislodgement into the left ventricle occurred mostly in male patients (39.47% vs. 11.82%). Furthermore, a higher incidence of adjusted in-hospital vascular complications (8.3% vs. 4.4%, P<0.001) and bleeding events (8.01% vs. 5.96%, P=0.06) as well as NACE (19.0% vs. 13.8%, P=0.06) occurred in the female cohort with no significant differences of death, MI, stroke, or MACE during the in-hospital period. Reaffirming data of the PARTNER A trial (13), women showed increased survival rates at one year after TAVR (78.7% vs. 75.5%, P<0.001).

Although the study’s results are not surprising and align with other previous studies (8,14,15), they illustrate the importance of gender variability in TAVR cohorts including a significant number of patients. While female gender has generally worse clinical outcomes as men in trials on percutaneous coronary interventions (PCI), coronary artery bypass graft surgery (CABG), and surgical aortic valve replacement (SAVR), it is of interest, that like in various other studies, female gender beats male gender in terms of an improved one year survival rate which this study underlines. This can be due to a different risk profile at baseline but also due to the fact that female patients are generally underrepresented in clinical trials on PCI, CABG, and SAVR.

By interpreting the results of Chandrasekhar et al. one needs to keep in mind that TAVR was used as a therapeutic option not only for severe aortic stenosis, but in >5% also for significant aortic regurgitation and bicuspid valves. The authors additionally underline the different cardiac risk profile between men and women. While arterial hypertension is known to have gender based differences in clinical outcomes (16), it unfortunately has not been separately listed and adjusted for. In terms of cardiac risk profile, the article sheds light on two frequently discussed assessment tools: first, the STS-score to determine the 30-day mortality and morbidity risk, which significantly differed between male and female patients in this study. However, this score was initially designed to predict surgical and not TAVR risk and moreover, attributes a higher risk to female sex. Thus, it should be used with caution when interpreting gender based differences in TAVR patients (17). Secondly, the frailty assessment, which—in the clinical context—is frequently carried out subjectively. Available tools to detect frailty showed no sex differences in TAVR patients so far (18,19). Nevertheless, frailty assessment should be handled with more care using these formal tools as early procedural risks may be overestimated resulting in a potential underutilization of valve replacement. As acknowledged by the authors, one limitation of the study is that no adjustment was performed for device types. With evolving technologies of valves, deployment and sheath systems, closure devices, as well as pending data on optimal anticoagulation therapy, gender based findings may change in the future.

In conclusion, this study adds to the existing body of literature finding explanations for gender-based differences in in-hospital as well as in one-year clinical outcomes after TAVR. Being able to understand which factors significantly contribute to an improved assessment and treatment strategy before, during, and after TAVR, further studies with a longer follow-up period are needed to fully understand the impact of gender. Moreover, this claim is underlined through the fact that unlike in PCIs, approximately 50% of patients undergoing TAVR are women (20). Within this framework, the importance of individualized patient assessments within a Heart Team cannot be overstated. Amongst others, it is here where good or bad outcomes are being decided.


Acknowledgements

None.


Footnote

Conflicts of Interest: The author has no conflicts of interest to declare.


References

  1. Holmes DR, Brennan JM, Rumsfeld JS, et al. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA 2015;313:1019-28. [Crossref] [PubMed]
  2. Kostkiewicz M, Tracz W, Olszowska M, et al. Left ventricular geometry and function in patients with aortic stenosis: gender differences. Int J Cardiol 1999;71:57-61. [Crossref] [PubMed]
  3. Bech-Hanssen O, Wallentin I, Houltz E, et al. Gender differences in patients with severe aortic stenosis: impact on preoperative left ventricular geometry and function, as well as early postoperative morbidity and mortality. Eur J Cardiothorac Surg 1999;15:24-30. [Crossref] [PubMed]
  4. Buchanan GL, Chieffo A, Montorfano M, et al. The role of sex on VARC outcomes following transcatheter aortic valve implantation with both Edwards SAPIEN™ and Medtronic CoreValve ReValving System® devices: the Milan registry. EuroIntervention 2011;7:556-63. [Crossref] [PubMed]
  5. O’Connor SA, Morice MC, Gilard M, et al. Revisiting sex equality with transcatheter aortic valve replacement outcomes: a collaborative, patient-level meta-analysis of 11,310 patients. J Am Coll Cardiol 2015;66:221-8. [Crossref] [PubMed]
  6. Généreux P, Cohen DJ, Mack M, et al. Incidence, predictors, and prognostic impact of late bleeding complications after transcatheter aortic valve replacement. J Am Coll Cardiol 2014;64:2605-15. [Crossref] [PubMed]
  7. Généreux P, Webb JG, Svensson LG, et al. Vascular complications after transcatheter aortic valve replacement: insights from the PARTNER (Placement of AoRTic TraNscathetER Valve) trial. J Am Coll Cardiol 2012;60:1043-52. [Crossref] [PubMed]
  8. Kodali S, Williams MR, Doshi D, et al. Sex-Specific Differences at Presentation and Outcomes Among Patients Undergoing Transcatheter Aortic Valve ReplacementA Cohort StudySex-Specific Differences Among Patients Undergoing TAVR. Ann Intern Med 2016;164:377-84. [Crossref] [PubMed]
  9. Humphries KH, Toggweiler S, Rodés-Cabau J, et al. Sex differences in mortality after transcatheter aortic valve replacement for severe aortic stenosis. J Am Coll Cardiol 2012;60:882-6. [Crossref] [PubMed]
  10. Hayashida K, Morice MC, Chevalier B, et al. Sex-related differences in clinical presentation and outcome of transcatheter aortic valve implantation for severe aortic stenosis. J Am Coll Cardiol 2012;59:566-71. [Crossref] [PubMed]
  11. D’Ascenzo F, Gonella A, Moretti C, et al. Gender differences in patients undergoing TAVI: a multicentre study. EuroIntervention 2013;9:367-72. [Crossref] [PubMed]
  12. Chandrasekhar J, Dangas G, Yu J, et al. Sex-based differences in outcomes with transcatheter aortic valve therapy: TVT registry from 2011 to 2014. J Am Coll Cardiol 2016;68:2733-44. [Crossref] [PubMed]
  13. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-98. [Crossref] [PubMed]
  14. Al-Lamee R, Broyd C, Parker J, et al. Influence of gender on clinical outcomes following transcatheter aortic valve implantation from the UK transcatheter aortic valve implantation registry and the National Institute for Cardiovascular Outcomes Research. Am J Cardiol 2014;113:522-8. [Crossref] [PubMed]
  15. Stangl V, Baldenhofer G, Laule M, et al. Influence of Sex on Outcome Following Transcatheter Aortic Valve Implantation (TAVI): Systematic Review and Meta-Analysis. J Interv Cardiol 2014;27:531-9. [Crossref] [PubMed]
  16. Vasan RS, Larson MG, Leip EP, et al. Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Disease. N Engl J Med 2001;345:1291-7. [Crossref] [PubMed]
  17. Ad N, Barnett SD, Speir AM. The performance of the EuroSCORE and the Society of Thoracic Surgeons mortality risk score: the gender factor. Interact Cardiovasc Thorac Surg 2007;6:192-5. [Crossref] [PubMed]
  18. Rodés-Cabau J, Mok M. Working toward a frailty index in transcatheter aortic valve replacement. JACC Cardiovasc Interv 2012;5:982. [Crossref] [PubMed]
  19. Green P, Woglom AE, Genereux P, et al. The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis: a single-center experience. JACC Cardiovasc Interv 2012;5:974-81. [Crossref] [PubMed]
  20. Mack MJ, Brennan JM, Brindis R, et al. Outcomes following transcatheter aortic valve replacement in the United States. JAMA 2013;310:2069-77. [Crossref] [PubMed]
Cite this article as: Vollenbroich R. Outcomes in patients undergoing transcatheter aortic valve replacement: a sex-based story of success? Ann Transl Med 2017;5(17):357. doi: 10.21037/atm.2017.06.02

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