The major findings of the present study were as follows: (i) increased LVWT was associated with a higher rate of AVR surgery, (ii) In patients with increased LVWT, the all-cause and cardiovascular death rates were both significantly lower in the AVR group than in the non-AVR group, and (iii) Increased LVWT was an independent predictor for cardiovascular death in patients with severe native AS.
Although the presence of extreme LVH in severe AS indicates poor prognosis, current guidelines do not consider LVH an indication for surgical replacement in patients with AS [9,10]. The indications for AVR are primarily based on the presence of clinical symptoms. However, the clinical symptoms of patients with severe AS are often difficult to differentiate from the symptoms of comorbid diseases, such as lung disease or coronary artery disease, in clinical practice. A few studies of severe AS have focused on the prognostic outcome of patients with higher LV mass or LVWT. In patients with severe AS, preoperative concentric LVH was associated with increased mortality after AVR [11]. Higher LV mass was related with worse clinical outcomes after transcatheter AVR in severe symptomatic AS [12]. In a prospective study, increased LV mass index was independently related with increased cardiovascular morbidity and mortality in AS patients [13]. In addition, increased cardiovascular mortality and morbidity have been reported for asymptomatic patients with severe AS and excessive LVH [14]. Thus, we believe that increased LVWT could be an important prognostic factor in severe AS, regardless of symptoms. Although LVH in severe AS is a compensatory phenomenon to reduce wall stress and maintain cardiac output [15], it eventually causes ischemia, fibrosis, and myocardial dysfunction [16,17]. Myocardial fibrosis independently predicts risk of mortality in patients with moderate to severe AS [18].
Increased LVWT and AVR
Because clinical decisions should be based on the risk of mortality, AVR might not a suitable endpoint in conservatively treated patients with severe AS. However, AVR is also the most important decision in the course of treatment for severe AS from a doctor’s point of view. In our study, the main causes of AVR were the development of symptoms (92/157, 58.6%) and LV dysfunction (29/157, 18.5%). Although LV hypertrophy was not considered a risk factor at the time of AVR, this retrospective study showed that patients with increased LVWT underwent AVR much more frequently than those without LVWT (60.1% vs. 39.0%, p = 0.001, Table 1). Furthermore, the cardiovascular death rate in patients with increased LVWT was significantly lower in the AVR group than in the non-AVR group (Figure 2B). These results imply that LV hypertrophy may be an important risk factor in AVR decisions.
Increased LVWT and mortality
The multivariate regression analysis in this study showed that increased LVWT was independently correlated with cardiovascular death in patients with severe AS. In this study, 108 patients (108/208, 51.9%) with increased LVWT had no or mild symptoms. In addition, 36 patients (36/125, 28.8%) with increased LVWT who underwent AVR had no or mild symptoms. This may imply that symptom-based decisions for interventions in severe AS might miss a chance for surgery in patients (about 30%) with no significant symptoms. Thus, LVH could be used as a more sensitive marker than symptomatic criteria for AS surgery decisions. Previous studies reported that LVH was associated with an increased rate of cardiovascular events in severe AS independent of other prognostic covariates, even in asymptomatic patients [11-14,19,20]. Recently, Kang reported that the incidence of cardiovascular death was significantly lower in those who underwent early AVR surgery than asymptomatic patients with very severe AS who received conservative care [21]. In our study, patients with increased LVWT had a 4.45-fold higher risk of cardiovascular death than those with normal LVWT. Interestingly, the predictors of cardiovascular death in this study were age, symptoms, AVR surgery, and increased LVWT, not LVEF. LV dysfunction is a well-known strong predictor of worse long-term survival, but our results did not agree with those of previous studies [22]. Although LV dysfunction caused by severe AS itself is a very important risk factor for cardiovascular death and a class I indicator for AVR surgery, LV dysfunction can develop from other combined valve diseases, or post-myocardial infarction. In our study, the LVEF was not significantly different between the AVR and non-AVR group. Additionally, most of the patients with LV dysfunction were symptomatic, and only four patients (4/125, 3.2%) had AVR surgery attributable to LV dysfunction itself (Figure 2). This implies that LVEF would not be a perfect indicator of AVR surgery in real practice. In contrast, increased LVWT was more common in the AVR group and showed statistical significance as a variable correlated with cardiovascular death. Furthermore, AVR surgery significantly reduced both all-cause deaths and cardiovascular deaths in those patients with increased LVWT. Thus, it might be a good additional index for AVR surgery decisions in patients with severe AS, in addition to symptoms. This study had limitations. First, because this was a retrospective study, the clinical data may be incomplete. Second, the follow-up period was clearly too short and the absolute number of patients was too small to have strong statistical power.