"Hello, I'm Nicolas Girard, I'm a professor of medicine in Nancy, France, in the Clinical Investigation center of Nancy. And today I will cover renal function decline before and after an hospitalization for heart failure in patients with HFrEF.

So we all know that the kidney is very important in heart failure. But actually the dynamic of heart failure renal function decline around heart failure [indistinct] is not well known. Three years ago in Paragon, very interesting results were published showing that actually renal function decline, a steeper decline of the EGFR started way before heart failure specialization, up to one year before. And we wanted to evaluate this in patients with HFrEF.

So we analyzed the dynamics of EGFR decline in several populations. First in trials, so ephesus and emphasis trials investigating the effect of MRA in patients with heart failure. Those were pooled together to have a larger sample. And we also evaluated this in the Barcelona Heart Failure cohort, which is a large cohort with a lot of biological evaluation, available in Spain. With this we have a blend of prior and real world evidence to see if this message is true regardless of the setting.

We wanted to show actually the renal function decline before and after heart failure [indistinct] or heart failure death. And we have plotted curves of this very precisely using complex modeling. And actually there was the surprise is that it's really replicating perfectly what has been shown in Paragon, even a little bit more association, meaning that you have a decline if you're before one year or after one year of the heart failure [indistinct], that is about 1 to 2 milliliters per minute per year, which is basically what you can observe in the general population. But when you look at the, the one year period before the decline is about 5 milliliters per year, which is very fast. And you observe that both in the trials and in the court and after the heart failure hospitalization, the decline is about 3. So those numbers are a little bit larger than what has been observed in Paragon. And this is perfectly aligning right. There is now strong evidence showing that EGFR decline starts way before the heart failure [indistinct].

This is a key question and this is not completely sure for now, our hypothesis is that under detected subclinical congestion occurs way before heart failure precision and is driving the EGFR decline. We have some evidence supporting this, mainly the fact that you can see NYHA classes increasing more than six months before heart failure [indistinct]. But we are not, there yet. We need to do additional analysis and having detailed, mediation analysis to see whether, this is mainly driven by congestion or by other factors. At this point, we cannot be sure.

We know kidney is important. We know renal function is important. We are measuring creatinine very frequently. But having a closer look to the dynamic of EGFR decline is probably a nice addition to clinical evaluation, because in those patients where you have a, steep, rapid EGFR decline, chances are, they have a higher risk of heart failure hospitalization. And this decline can be actually one of the first hints of, higher heart failure risk. So this is relatively new, and we should implement this, probably in our, thinking, in clinical reasoning, for example, during a consultation.”