About half of all patients experience renal improvement immediately after TAVR in our study. For most patients, this does not have a clear effect on survival. However, in one specific subgroup, survival was markedly decreased if patients did not achieve renal improvement. These patients in quintile 5 of our propensity score, which represents the highest likelihood for RI, can be characterized as being mostly female, having poor initial renal function (high creatinine and low eGFR), significant comorbidities and more severe symptoms (higher NYHA class, higher STS score, higher initial NT-proBNP), and having shorter overall-survival time. RI in this subgroup increases survival to that of patients in lower propensity score strata (i.e. with better initial prognosis).
Propensity score methods are common approaches to minimize the effects of confounding when estimating the effects of a potential risk factor in an observational study. We used stratification on the propensity score such that five equally sized groups were analyzed conceptually both as a meta-analysis and for each stratum individually. It was demonstrated that stratifying on the quintiles of a continuous confounding variable eliminates approximately 90% of the bias due to that variable [15]. The factors used in this score were clinical and laboratory parameters for the assessment of cardiac and renal function as well as relevant cardiovascular comorbidities and established risk-scores.
There are several possible explanations why patients in propensity score stratum 5 benefitted most from RI despite the higher morbidity compared to patients in lower propensity score strata. One aspect might be that these patients had the most severe pre-existing chronic kidney disease and thus improvement had the highest impact in this group. Another factor could be that improved hemodynamics after TAVR leads to a better kidney perfusion and thus addresses an underlying functional deficit that is potentially reversible as opposed to a more structural kidney damage. Interestingly, the BMI was higher and the rates of dyslipidemia and diabetes mellitus were significantly lower in the propensity score stratum 5. These factors by themselves are well established risk-factors for the development of a structural chronic kidney disease (e.g., diabetic nephropathy) which would not respond as well to improved hemodynamics as a functional impairment alone. It is well established that chronic kidney disease is linked to an exponentially increased absolute risk for mortality with decreasing renal function as shown in a meta-analysis from 2006 [19].
Another hypothesis could be that not all patients benefit from TAVR in terms of improved hemodynamics. Voigtländer et al. [18] showed an improvement of cardiac output in patients with an increase in eGFR after TAVR, but not in patients with a decline in eGFR. In addition to that, an association between renal perfusion index and cardiac left ventricular systolic function has been previously shown [20].
Moreover, both renal and cardiac fibrosis are promoted in the setting of chronic cardiorenal syndrome via multiple pathways [21]; improvements in hemodynamics after TAVR could thus slow down the progression of a structural chronic kidney disease.
In propensity score strata 1–4, we also detected improved survival in patients without RI when comparing the data to stratum 5. This finding is not surprising. As described above, the propensity score for RI was calculated to create patient groups which are comparable regarding potential confounders. As a result of this propensity scoring, patients in higher strata not only have a better chance for RI, they also have higher rates of factors for adverse outcomes such as higher age, higher NYHA class and higher initial NT-proBNP. What is intriguing about this finding is that the decreased survival in patients was only seen in patients without RI. Patients with RI had similar, much higher survival regardless of the propensity score stratum. RI could thus define a lower risk subset of patients.
Of note, in highly symptomatic patients (belonging to NYHA class IV), renal improvement was associated with significantly improved survival. There are various possible explanations to this specific finding. In addition to the aspects discussed above, patients with higher stages of chronic heart failure are dependent on their heart failure medication to improve morbidity and mortality. Recent studies have shown that lower eGFR was associated with higher rates of adverse reactions of heart failure medication that lead to drug discontinuation [22]. The improved survival in patients with NYHA class IV and RI could thus at least in parts be explained by higher rates of drug adherence. Further studies will be needed to address this finding.