Robert Montgomery, MD, discusses the novel approach to ADHF management.
these are fantastic talks and it's an honor to be on stage with you guys. I guess I'm gonna be talking about the chick fil a and what the effect of that is. So we'll talk about the role of salt and acute heart failure. I'm going to tell you the evidence as best I can and some new evidence provided that we presented at a week and a half ago. I just gotta take it as a dictator on heart failure Service. All my patients are on a two g sodium restricted diet. I'm just going to assume that most of your patients who come in with heart failure are the same. And so we place patients with acute heart failure on the sodium diet. And the question is, should we? And I think everyone's gonna make up their own mind about it. Uh okay, so I think before we start saying about other issues, why does it make sense? Why do we do it? And I think it makes sense physiologically. So this is a total body volume distribution. If you look at where salt is none of it really into intracellular compartment all of it's pretty much in your interstitial and intravascular component. And so all that salt and all that water, six year old can probably tell me that sort of water follows salt. And so when you look at what happens, when you put 10 kg of fluid onto a patient, very little that goes into interstellar spot. But all that salt, about half your total bodies, you can double the amount of sodium in your body and all that sodium goes into the interstitial space. And so when you add that much of a salt, it's going to fill up your interstitial fluid in your intravascular volumes. We have outpatient experience but just sort of following people observation early that sort of says that a high sodium diet is associated in ambulatory heart failure, patients with increased readmissions. This is an uncontrolled, just observational data and that sort of guided a lot of our thinking and how we treat patients. But it's not without concerns the effect of sodium restricted diet. When you decrease sodium you decrease calories, you decrease carbohydrates for whatever it's worth. And then you can decrease calcium thiamine folate sodium restriction. It's very hard to actually decrease sodium without affecting other nutrients. Um you know, we spent a lot of time talking about adherence to diet, but when you actually look at why people come into the hospital, it's actually one of the issues that, you know, there's other issues of schema, arrhythmias, pneumonias, inflammatory issues, driving a lot of those presentations even though we kind of often think about is that this chick fil a and so all these things neuro hormonal activation, inflammation in the field dysfunction, all of those can end up affecting fluid shifts your spanked inactivation peripheral vessel constriction, all of that can lead into acute heart failure and so sodium is just one part of that. If you actually look at what happens on other metrics of what happens to patients who are on sodium restricted diet, what happens to the financial attention activation system. The reason goes up how doctorow goes up there all increased in sodium restricted patients. The concern only when you actually look at other trials that have or observation data, this is from the heart failure, art or fart study. There was a trend towards increased deaths and increased heart failure, hospitalizations with low sodium diets. And when you look at meta analyses looking at low sodium diets and patients, there's a trend that a low sodium diet has not been shown to improve mortality Thankfully. The sodium HF trial which is an outpatient trial just completed which randomized 806 patients across multiple sites. And they didn't see harm significant harm associated with sodium restriction in the outpatient setting. But they saw some improvements in quality of life scores but no improvements and all cause mortality. No improvements in cardiovascular hospitalizations and maybe you know, I'd say no significant increase in E. D. Visits. Though there was a slight increase in the group. The only randomized evidence in the inpatient setting to back any of our data is there's two trials from brazil that also looked at fluid restriction at the same time. They restricted patients to less than 800 mg of sodium a day compared to a 3 to 5 g sodium diet, 75 patients. And they found no difference in time to de congestion clinical congestion scores, changing weights. And they did see an increase in thirst in the sodium restricted group. And so all that data that we haven't found really evidence of benefit. There is concern about angiotensin activation. What about giving salt? Has anyone been crazy enough to do that? And so there is data. That's actually quite impressive data. Maybe too impressive in some ways. But giving hyper tonic saline to patients with acute heart failure. This was done at multiple centers in Italy. They took 1771 patients as the Smack HF trial with patients with acute heart failure and gave them hyper tonic sailing. They randomized them to get 150 ml to 4% to 4.6% of sodium chloride twice a day. They gave him 250 mg of Lasix twice a day. There's a difference in the amount of sodium that gave them their diets and they restricted them to a leader of fluid. So these are the difference is the difference between getting 1800 mg of sodium chloride versus 12 g of sodium chloride. They saw that you peed more with hypersonic saline, your renal functions better with hypersonic saline, your length of stay was shorter with hypersonic sailing. Very convincing. Uh They also showed a mortality benefit. Uh you know, when you gave hyper tonic saline, there was less deaths less readmissions. I would say that that trial may be a little, it has not been replicated at nearly the same things. And so there's questions about that authors group. But that trial still stands at the moment and that's probably the best evidence for hypersonic sailing at the moment. So the questions like why would you give salt? And I think we know, you know, when you look at the diuretic effect of the trade entry drugs from Hiroshima back to 1966 we know that the more Lasix you give, the more salt G. P. But that's only temporary. You're gonna pee a lot in those first few hours. And then they knew the very first study on somebody says it loses its effectiveness. You're gonna pee less sodium with time and more diuretic exposure. And so if you look at patients who are admitted to the heart to the hospital and see how much salt you actually lose, you can lose in the first day, 42g of sodium chloride um, you can lose basically half of that extra salt. You know, if you have 100 50 miles a third of the amount of salt in your body you can lose in one day, that's what the hyper responders, the highest tactile, but the lowest responders will lose much less. And so we know that even the people who lose the most salt that trails off over time. And so if you actually look at what's happening with your memory, lie that your kidneys sensing that salt and as it senses less and less salt, it's gonna pull on to sort of ramp upbringing and your attention activation to try and hold onto sodium. And if you give the thought process of get hyper tonic saline that blocks that effect and you can keep on going with your diuretics. And so I'm just going to summarize it before I tell you what we did with our study. You know, this is a very common situation that's happening sort of 3000 times a day, a million times a year of choosing those things. It makes sense potentially just mechanistic Lee and observation early to decrease the amount of salt, decrease the number of heart failure admissions can there's concerns about nutritional quality reading a genetic activation. There's only one real single randomized trial from the same group, You know, with a total 75 patients didn't show effect. And there may be some benefit for getting hyper tonic saline. So what do the guidelines say? Surprisingly, despite the ubiquity of study restriction and the hospital, there's actually no recommendation, acute heart failure on stage. So it's reasonable to a but classy level of evidence and heart failure. And the european Society of guidelines doesn't give any recommendations. They just sort of say in patient education, just don't take too much salt. But there's no formal recommendation. They all say dietary sodium and sodium restriction is a significant evidence gap. So to address this, myself and my colleagues here, we designed this trial called oral sodium to preserve renal efficiency or osprey in acute heart failure. And so we decided there's no placebo double blind trials in salt that I'm aware of in this. And so we decided to sort of see if we could do a double blind placebo controlled trial to look at what the effect of salt and acute heart failure is. And so we want to know the short term the short term safety of giving salt when you're getting diabetics, marrying some of the effects of hyper tonic saline and looked at the change in weight change the renal function in 96 hours. We took 18 year olds made to our cardiovascular medicine floor you had to have an anti appropriate p greater than 1000 people. We want to see what the effect is really when you're being diaries. Not when you're stable. And so we chose people who were diuretic resistant. We felt like because they're on a LASIK strip at 10 mg an hour. And we tried to exclude people who were just about to be discharged significant changes in your sodium A. C. S. If you're going to be on dialysis or was really low. We didn't include you. And then if you couldn't take the pills or absorb the pills you didn't get it. This was at a single center. We did an internal funding we turn during the covid epidemics of the amount of outside hospital food was pretty much minimal. Um and we gave two g of sodium chloride or placebo three times a day during while you're getting an ivy diuretic. And we stopped if you didn't weren't getting an ivy diuretic and addition to the two g sodium diet that everyone got. So how much is this? This is six g of sodium a day. This is a hypersonic saline, has about 4.5 g of salt. And if you go to McDonald's and you order a large fry you can get six of them before you get what we got in a day. So if that gives you some reference of what you'd be a conservative if you saw that in your patient's room. And so we chose a binary outcome of changing karate and changing weight 96 hours. This is a semi controversial end point because it's not too clear that sort of worsening renal function and acute diabetes is bad, but the true effect of improving people's renal function with hyper tonic saline. We wanted to test, we felt that 70 patients was adequate to sort of look for a pretty large effect. This is a small study. And so we randomized 70 patients five withdrew, none of them withdrew for any sort of adverse event. But just because these pills that we gave them a pretty ginormous and these are the patient patient characteristics. This is a very busy slide. You're not gonna be able to read it. And so the average patient was 70 years old. White male with hypertension obesity. They had an average of around 45%. And they've been hospitalized twice in the past year and were being treated with the 15 mg and our basic strips. They weren't overly hypertensive. They were obese and they were reporting moderate about thirst. Uh Their labs were notable for the average G. F. R. Was 39. They're mildly anemic. Their anti pro BMP was around 4000. They were not on inhibitors not SGL T two S. They were on beta blockers. Spironolactone hydrolyzed its orbit. It's a sick group. I would not just between the group. There's a slight difference in our serum creatinine between the two groups though the estimate was not statistically different. And at 96 hours after giving out an average 13 g of sodium chloride to very sick patient population, we saw no difference. Both groups lost weight. Both groups had a slight increase in their crowning. And so I was worried when we actually looked at these results back in july 5th was like maybe they didn't absorb the drugs. And because we saw really no difference until we looked at there's two things that we saw. One is that serum sodium was just basically between the groups that falls with diaries owes but it falls less. Pretty much negligible. E in the group was certain chloride and the increases in both groups with di recess but it increases less in the sodium chloride treated groups. The U. N. Has been treated in the past as sort of like sort of a marker of angiotensin activation. We saw no safety events. That was significant difference between the two groups. And I would also say we're not trial. You would need a much bigger trial to actually see that. And so this is a single center study. This is only a subset of acute heart failure population only treated while they were getting diuretics. But and I'd say that even though we didn't see benefit we can't really there's something different about hyper tonics alien that there's an osmotic load to it too. So it's not exactly equivalent. And there was a power issue. We weren't powered fully for weight change because it was a bigger display than we expected. But if you want to look for what's the double blind placebo controlled trial or evidence for acute heart failure. That's it. Um and so if you get 13 g of sodium chloride we didn't see any significant difference in this group. And except for sort of these changes in view and creatinine. And so my takeaway is that I would when I sort of see the two g sodium diet on my patients. I have not changed their diet unless they complain about it. You know it's a it's a culture change a little bit. And so you have to think about how the electronic medical record biases our choices. But I think it's also where I don't when you can devote your time towards these devices towards quadruple therapy. I think that's where we should be spending our time. And so I think we can definitely do larger trials on this. And I think that's to be seen. So I'd like to sort of think that people are helped out with this trial. And thank you.