Hi, I'm Faiez Zannad. I am an Emeritus Professor of Cardiology and Therapeutics in University of Lorraine in France. And my main interest is heart failure. Americans would say I'm a heart failure doctor. There isn't such a specialty here necessarily in Europe, but this is the area where I spend most of my time: heart failure care and heart failure clinical trials—building the evidence with the main therapies for heart failure, whether it is HFrEF and HFpEF, which has been the main evidence where the guidelines were built on. So certainly, generating guidelines from evidence is one of my important areas of interest.

What are the main barriers to creating integrated guidelines for CKMD?

Well, the main barrier is certainly the chronic kidney and metabolic disease concept because we have been living in silos for long. There have been the heart failure trial, the heart failure docs and the nephrologists, the diabetologists and the obesity doctors. And we all lived in different silos. And actually even the trials were diabetes trial were, you know, heart failure trials.

And it's only recently then when we had, you know, hijacked some of the diabetes medication like the SGLT2 inhibitors, and now recently some obesity medication like GLP-1 receptor agonists, that we realized that actually heart failure is so common across the spectrum of metabolism and also kidney disease. This is something which we need to convey further and just making sure that these are the same patients and that the guidelines should be really constructed on not only the evidence of medication, but the evidence of about how to screen for the additional condition.

Certainly most cardiologists would not necessarily screen for CKD, and certainly albuminuria has been in the textbook for a while, but not so many general physicians or cardiologists are screening for albumuria in patients with heart failure, for example. The other way around, diabetologist or nephrology would not necessarily screen for heart failure, would not necessarily perform an NT-proBNP testing on echocardiography. So this is the main barrier silos that we have been living in for years, but now the message is getting through.

And certainly the new neologism of CKM—it's very important that has been created by the American Heart Association. I mean, almost concomitantly to this publication of the American Heart Association, I have published with Dr. Carmine Zoccali the same concept in another journal, in the nephrology journal, we came out with another acronym, not CKD but CHKD: chronic heart and kidney disease. So getting this single entity is the main barrier. But we are moving forward and we ought to be getting there.

When you envision simpler guidelines, what key changes would you say are required?

Well, simpler guidelines should be managed by, meant to be targeted for general physicians because general physicians, the doctors will see the patient from different perspectives from their heart, the kidney and metabolism perspective. I'm afraid that the different specialty and organ-specific specialty are still very much siloed and including their guidelines. So maybe we should have an overarching guideline across all these specialty and which necessarily would need to be made simpler because the current guidelines are still just too much sophisticated. And the key changes is indeed making them simpler, making them straightforward for implementation and maybe built around different scenarios because the scenarios are still differing whether the patient presents as a heart failure as a first manifestation or as a CKD as the first manifestation or as a diabetes.

So depending on where the patient enters the care from the first manifestation, the first simple guideline and advice should be screening for the alternative condition. It's bound that most patients with heart failure, if you screen for CKD you will find CKD, right? If you screen for albumuria and for glucose control, many of them will have pre-diabetes or something. So this is the simplest message we need to convey.

How might integrated guidelines help address the challenge of therapeutic inertia, particularly in patients with multiple CKM conditions?

Well, this is a really very important question: integration of guidelines. The integration of guidelines is still an unmet need, and it is the highest need because inertia is mainly driven by concern about safety, and safety usually driven by the other organ.

Now let me explain. The cardiology and heart failure specialists are mostly concerned about hyperkalemia and worsened renal function, for example. And they are concerned about the kidney. So we need to educate them that you really need to use the life-saving medication no matter how EGFR might rise because this is inevitable that many medication upon initiation will have some rise in creatinine, a drop in EGFR.

So therapeutic inertia is mostly driven by safety and blood pressure lowering, hyperkalemia, worsening renal function. So integration of guidelines or maybe in patients with metabolism, diabetes by hypoglycemia with the concern from cardiologists that hypoglycemia may indeed worsen the cardiac prognosis. But this is indeed the integration of this single entity syndrome of CKM, which may be helped by integrated guidelines which may educate doctors better about the excessive concern they are having about safety, and therefore, make integration and implementation much simpler and inertia less than rule.

Are there any specific examples where current separate guidelines might give conflicting recommendations for patients with multiple conditions, and how integrated guidelines could resolve these conflicts?

Yes, one of them is hyperkalemia and worsening renal function. Well, I wouldn't say that actually separate guidelines give conflicting recommendations because across the board the recommendations are very similar. I mean, if anything, nephrologists are much more flexible and better than cardiologists in not much worrying about some drop in EGFR, for example, and some increase in potassium because they know how to cope with that and they know that the prognosis, cardiovascular renal prognosis, which is improved by drug therapy, it's much more important than the very small risk related to this hyperkalemia or worsening renal function.

So this is one specific example where better communication across specialty may help. I wouldn't say that, we can certainly learn from each other, and nephrologists may feel much more comfortable having cardiologists encourage them to screen for heart failure and not being much worried about the cardiovascular consequences of their drug and vice versa. So it's fostering communication among specialty which is really the biggest unmet need. But progress is there because this concept of CKM is moving forward, and the trials actually has made wonderful progress.

In the early, maybe 10 or 20 years ago, low EGFR was an exclusion criteria for most heart failure trials. Now, hopefully, the latest trial we got patient enrolled in trials with EGFR as low as 25 and 20. So generalized results are made easier and the same thing when it comes to diabetes or nephrology trials. They are no longer excluding patients with some sort of signs or symptoms of heart failure, so that integration is on the move. And that's the main educational message. It educates people that at the end of the day the same patient who may have cardiac, kidney, and metabolism issues.

Where do you see the future of CKMD guidelines going?

Well, as I've said, I mean having a single set of CKM guidelines would help much. For the time being, we still, although there is a real good consideration of all the holistic management of the patient, but we still have KDIGO guidelines, we still have AHA and ACC guidelines and ESC guidelines. So cardiology guidelines, diabetology guidelines, although each of them actually does consider really the points that I have highlighted, they do focus on, although these are nephrology guidelines, there are many points of discussion about management of the cardiac condition and management for diabetes and vice versa.

But one keeps, you know, wondering why is it that we have so many separate guidelines. So I'm really wishing that at some point we have CKM, single CKM guidelines, all endorsed by all this specialty across the board because we are just being redundant with very similar guidelines from different organizations and learned societies. So the future is integration and desiloing, breaking the silos. That's the most important.

I would like, just to add a final word actually, which is going beyond CKM and integrating the liver. And, therefore, I'm now advocating for CKLM — chronic cardiac, kidney, liver metabolism disease — because MASLD, as we call them, steatosis in the liver, is very much part of the picture. And all these conditions are consubstantial, they all stem from the same risk factors, which are hypertension, obesity, diabetes, et cetera. Most of them are the result of progression across very similar underlying mechanisms: inflammation, fibrosis are some of them. And the renin-angiotensin as a system is part of these different mechanistic pathways. And by the ending up by developing these multiple diseases and patients get into different silos only depending on which specialty they will meet first and what is their first clinical presentation. So adding again a metabolism and the liver dimension would also need to be the next challenge.