While patterns of upstream cardiac damage do differ between the sexes, a staging classification proved effective in the stratification of 5-year outcomes in both women and men with aortic stenosis (AS), according to a new analysis of patient data. Led by Masaaki Nakase, MD, from the University of Bern, Switzerland, the team noted that before the advent of transcatheter aortic valve replacement (TAVR), a notable sex-related disparity existed in access to AVR, with fewer women than men undergoing surgical intervention. “This discrepancy has been attributed primarily to advanced age, increased frailty, and a higher risk of procedural complications in female patients,” said the team. “Consequently, women experienced a higher likelihood of undertreatment, ultimately resulting in more advanced cardiac damage because of long-standing pressure overload caused by AS and adverse prognosis.” While the advent of TAVR effectively mitigated such historical sex-related disparities in access to treatment of AS, recent meta-analysis data have suggested that women undergoing TAVR had lower long-term mortality compared to men, potentially attributable to a longer life expectancy and fewer comorbidities in women. Writing in a study published online Monday and in the May 27 issue of JACC: Cardiovascular Interventions, Nakase and colleagues noted that noted that cardiac damage caused by AS can be categorized into stages that are associated with a progressively increasing risk of death after TAVR. “Given the sex-specific differences in myocardial remodeling to AS and the influence of sex hormones on pulmonary vascular resistance, the accumulation of cardiac damage and its prognostic value may differ between the sexes,” they suggested. Study details Nakase and colleagues investigated sex-related differences in cardiac damage among patients with symptomatic AS and the prognostic value of cardiac damage classification in women and men undergoing TAVR. In a prospective registry, pre-TAVR echocardiograms were used to categorize 2,026 patients (995 women; 1,031 men) undergoing TAVR into five stages of cardiac damage caused by AS, said the authors, adding that differences in the extent of cardiac damage were compared according to sex, and its implications on clinical outcomes after TAVR were explored. “We observed sex-specific differences in the pattern of cardiac damage,” said Nakase and colleagues, noting differences in cardiac damage between men and women at all stages – Stage 0 (2.6% women vs 3.1% men); Stage 1 (13.4% vs 10.1%); Stage 2 (37.1% vs 39.5%); Stage 3 (27.5% vs 15.6%); Stage 4 (19.4% vs 31.7%). Furthermore, they revealed a stepwise increase in 5-year all-cause mortality according to stage in women (adjusted hazard ratio [HRadjusted]: 1.43; 95% confidence interval [CI]: 1.28-1.60, for linear trend) and men (HRadjusted: 1.26; 95% CI: 1.14-1.38, for linear trend). In the overall population, women had a lower mortality than men (HRadjusted: 0.78; 95% CI: 0.67-0.90; P < 0.001), the researchers added, noting that the trend was consistent across early stages of cardiac damage including stage 0 or 1 (HRadjusted: 0.56; 95% CI: 0.32-0.98; P = 0.043) and stage 2 (HRadjusted: 0.75; 95% CI: 0.58-0.97; P = 0.027). However, there was similar mortality between the sexes in advanced stages of cardiac damage, including stages 3 (HRadjusted: 0.92; 95% CI: 0.67-1.27; P = 0.625) and 4 (HRadjusted: 0.87; 95% CI: 0.66-1.14; P = 0.297), they said (P for interaction = 0.394 among all stages and P for interaction = 0.075 between early and advanced stages). “Although the distribution of the stage of cardiac damage varied between sexes, the staging classification stratified mortality after TAVR for both women and men,” they said, adding that while women had favorable prognosis compared to men in early stages of cardiac damage, women in more advanced stages had comparable mortality to men. “It is essential to identify patients with AS in early stages of secondary cardiac damage and perform TAVR before progression to more advanced stages regardless of sex,” they concluded. A ‘pivotal message’ Writing in an accompanying editorial comment, Giulia Costa, MD, PhD, and Cristina Giannini, MD, PhD, both from Azienda Ospedaliero-Unversitaria Pisana, Pisa, Italy, said the study provides a thorough analysis of sex-related disparities in cardiac damage across different stages of AS, as categorized by the Généreux classification, and their influence on outcomes after TAVR. The study found that female sex was associated with reduced mortality in the initial stages (0-2) of cardiac damage, but this advantage was not observed in the more severe stages (3 or 4). However, the editorialists warned hat a “pivotal message” arises from the results, in that the increase of mortality across all stages of cardiac damage was evident for both sexes. Moreover, they noted that the advantage of female sex was lost in patients with a low-flow/low-gradient phenotype – “even if the strength of this association might be hampered by the small number of patients in this subgroup.” “If TAVR is the treatment of choice for our patients, it has to be done early,” they warned. “Treat women early, so they can enjoy the perks of fewer comorbidities and overall better outcomes. Treat men early, so they do not experience the dismal prognosis of advanced cardiac damage,” they said. Sources: Nakase M, Tomii D, Maznyczka A, et al. Sex-Specific Differences in Upstream Cardiac Damage in Patients With Aortic Stenosis Undergoing TAVR. JACC Cardiovasc Interv 2024;17:1252-1264. Costa G, Giannini C. The Sooner, The Better! JACC Cardiovasc Interv 2024;17:1265-1266. Image Credit: Vitalii Vodolazskyi – stock.adobe.com