Patient characteristics
Patient characteristics are presented in Table 1. The study cohort consisted of a total of 466 Patients with AS who underwent TF-TAVR between the years 2009 and 2016. The median age was 81 years, a total of 200 patients were male (42.9%). 49 Patients had an LVEF < 35% (10.5%), the majority of patients (n=328, 70.4%) suffered from severe dyspnea (NYHA classes III and IV). Patients exhibited comorbidities such as coronary artery disease (n=327, 70.2%), arterial hypertension (n=422, 90.6%), history of atrial fibrillation (n=204, 43.8%), dyslipidemia (n=228, 48.9%), and diabetes mellitus (n=141, 30.3%). A large proportion of patients had preexisting chronic kidney disease, as measured by preprocedural creatinine and eGFR. Values for NT-proBNP and hsTNT were also elevated. The median logistic EuroSCORE the EuroSCORE II, and the STS score.
Frequency of renal improvement
According to our criteria described above, RI after TAVR was observed in 255 (54.7%) of a total of 466 patients. Patients with RI were generally slightly older (median 82 vs. 81 years, p=0.006), more frequently female (62% vs. 51.2%, p=0.019) and had slightly lower BMI (median 26.01 vs. 26.77, p=0.049). They also had higher EuroSCORE II (median 4.66 vs. 3.92, p=0.01), lower eGFR (median 49 vs. 57, p=0.001), higher creatinine (median 103.55µmol/l vs. 96.55µmol/l, p=0.021), and higher urea (median 7.7 vs. 6.8 mmol/l, p=0.01) at baseline compared to patients without RI (Table 1). Among the subgroup of patients with RI, the median improvement in creatinine was 12%, and 75% of the patients had an improvement of at least 6%.
Description of propensity score quintiles
Detailed patient characteristics for each propensity score quintile are summarized in Table 2. These quintiles reflect the monotonous increase in the likelihood of RI, with a frequency of 36.2% in the lowest quintile to 73.1% in the highest quintile. Patients in higher propensity score strata were older and more often female, had a higher NYHA class, higher initial NT-proBNP, and a higher rate of atrial fibrillation which is generally associated with poorer prognosis. Interestingly, there were fewer patients with diabetes mellitus and dyslipidemia in higher propensity score strata.
Association of RI with survival
In the total cohort, survival time did not differ between patients with or without RI (adjusted for propensity score strata, p=0.13). However, there was a statistically significant benefit in the survival time of patients with RI (vs. those without RI) in propensity score stratum 5 (Figure 1, p=0.002, HR=0.32, 95% CI=[0.15-0.69]), whereas no significant difference in the survival time could be observed for patients with RI vs. those without RI in the individual propensity score strata 1-4 (supplementary figures 1-4; p > 0.17 for all strata). The same risk group was identified in the complementary comparisons: in the subgroup of patients without RI, there was a significantly decreased survival time in propensity score stratum 5 compared to strata 1-4 (p<0.001, HR = 2.93, 95% CI= [1.58-5.46], supplementary figure 5), whereas there was no significant difference among patients with RI (supplementary figure 6). Thus, only one group of patients had a markedly poorer prognosis than all others: those in stratum 5 who did not achieve RI had an estimated two-year survival rate of only 43.9%, while patients in all other subgroups (stratum 5 with RI and strata 1 to 4 irrespective of RI) had estimated two-year survival rates of 75.7% (between 64.8% and 85.5% in individual subgroups, see supplementary figure 7).
Interestingly, in the highest NYHA class (IV; n=50 patients; of these, 27 were in propensity score stratum 5), RI was associated with a significant increase in survival time (p<0.001, Figure 2, HR = 0.15; 95%-CI= [0.05-0.44]), whereas patients with RI in NYHA classes II and III showed no statistically significant improvement in survival time compared to patients without RI (p>0.8, supplementary figures 8&9). Similarly, patients in the highest quartile for NT-proBNP with RI showed a significantly longer survival compared to patients without RI (p=0.04, Figure 3, HR = 0.53; 95%-CI=[0.29-0.98]), whereas patients in the lower quartiles 1-3 for NT-proBNP showed no difference in survival depending on RI (p=0.87, supplementary figure 10).
In our first sensitivity analysis, the Cox regression model showed a significant effect of RI (p=0.02) when interaction terms between RI and NYHA as well as between RI and NT-proBNP (NYHA*RI: p= 0.04, NT-proBNP*RI: p = 0.0015; supplementary table 2) were included in the model. Further sensitivity analyses confirmed the robustness of the survival benefit of patients with RI in propensity stratum 5 and in the subgroup of patients with NYHA class IV, using different definitions of “RI” based on larger improvements (5% or 10%) of either serum creatinine or eGFR with similar estimated HRs (see supplementary table 3). The survival benefit in the subgroup of patients with elevated NT-proBNP (baseline values in the upper quartile) was not as clear in the sensitivity analyses.