2021 年 85 巻 7 号 p. 989-990
Chronic left ventricular (LV) pressure overload due to severe aortic stenosis (AS) leads to cardiac remodeling, of which LV hypertrophy (LVH) is the most important structural alteration.1,2 Initially, LVH was thought to be a compensatory or adaptive process to maintain cardiac output in the face of elevated afterload by decreasing LV systolic wall stress according to the law of Laplace. However, in some patients, probably when the LV mass exceeds a certain threshold, maladaptive LVH may cause diastolic dysfunction, adverse intramyocardial fibrosis, and even systolic dysfunction in a certain number of them, leading to heart failure.1,3 Relief of LV pressure overload, either with surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI), leads to substantial LV mass regression, which might be associated with clinical outcomes.4,5 Namely, greater LV mass regression might lead to better outcomes. Sex-associated differences in the phenotype of LV remodeling have been reported in patients with AS.6,7 Furthermore, multiple reports have described differences in clinical outcomes following TAVI by sex.8,9
Article p 979
In this issue of the Journal, Shishido et al10 investigate sex-associated differences in the long-term prognosis of Japanese patients who undergo TAVI for severe AS. Their retrospective study included a very large number of patients (n=2,588) enrolled in a multicenter registry. They demonstrate that women have a better prognosis than men in terms of all-cause and cardiovascular death. Female sex was an independent predictor of better prognosis, in addition to preprocedural New York Heart Association (NYHA) class, chronic kidney disease, Society of Thoracic Surgeons (STS) mortality score, and alternative vascular access. They analyzed the sequential changes in LV mass regression, which were similar between women and men throughout the 2 years following TAVI. Although women had better clinical outcomes, LV mass regression was similar between sexes. Furthermore, their study included a very interesting subgroup analysis: sex-associated differences in outcome were observed only among patients with LV mass regression. In contrast, sex-associated differences were not observed among about one-quarter of patients, male or female, who did not experience LV mass regression.
Regarding LV mass regression following TAVI, Chau et al5 recently published a very powerful paper. In patients undergoing TAVI with a balloon-expandable heart valve enrolled in the PARTNER (Placement of Aortic Transcatheter Valves) trials, long-term outcomes up to 5 years were clearly associated with the extent of LV mass regression at 1 year after TAVI (Figure). Although sex-associated differences were not described in detail, the postprocedural distribution of LVH severity at 1 year was similar between women and men. If these results regarding LV mass regression had been observed in the study by Shishido et al,10 women would have likely experienced more LV mass regression than men. What should we think about this discrepancy?
Time-to-event curves from 1 to 5 years for cardiovascular death or rehospitalization based on quartiles of left ventricular (LV) mass index regression from baseline to 1 year. Quartile 1 exhibited the least and quartile 4 the most regression in LV mass index at 1 year after transcatheter aortic valve replacement (TAVR). Percentage of patients with residual LV hypertrophy (LVH) and the adjusted risk for clinical outcomes. CI, confidence interval; CV, cardiovascular; HR, hazard ratio. (Reproduced with permission from Chau KH, et al.5)
There is a striking difference in the patient population of these 2 studies. In the study by Chau et al,5 subjects were restricted to patients with preprocedural LVH of moderate severity or greater. In contrast, in the study by Shishido et al,10 all eligible patients with or without LVH were included; 21.8% of their study participants did not have LVH before the procedure; they had normal or concentric remodeling LV morphology. Consequently, the proportion of patients without LVH at 1 year after TAVI was much greater in the study by Shishido et al10 than in the study by Chau et al5 (women: 32.1% vs. 22%; men: 58.0% vs. 21%). In particular, male subjects in the study by Shishido et al10 included as many as 35.6% patients without preprocedural LVH, which might obscure the relationship between LV mass regression and clinical outcomes. Nevertheless, sex-associated differences in clinical prognosis among patients with LV mass regression suggest some important points. Although women are expected to have greater longevity than men, the higher prevalence of comorbidities in men could affect this result. Namely, some comorbidities that were more prevalent in men such as diabetes and previous stroke, which were not statistically significant (P>0.05) but borderline significant (P=0.092 and 0.076, respectively) predictors for all-cause death in the univariate Cox proportional hazards models and consequently not included in the multivariate model, could have had a negative effect on prognosis. Even after successful TAVI, we should never forget that the optimal management of comorbidities is critically important. Furthermore, about one-quarter of patients did not have LV mass regression following TAVI, which is in line with the study by Chau et al.5 There are numerous other factors related to persistent LVH;1,11,12 however, we should also never forget that some of these factors, such as metabolic diseases like diabetes and systemic hypertension, are targets for proactive intervention.
Along with surgical aortic valve replacement, TAVI has now become the standard treatment for AS. TAVI is increasingly performed at an early stage.13,14 Therefore, subsequent patient assessment and optimal management of cardiac and other comorbidities will become more important for postprocedural care of patients who are treated by TAVI.
